90097-52-2Relevant academic research and scientific papers
Quinoline and 2-nitroimino-1, 3-diazacycloalkane hybrids: Design, synthesis and insecticidal activity
Sowmya, Jonnalagadda,Padma, Banda,Leelavathi, Panaganti
, (2021/12/09)
A library of new hybrid molecules comprising quinoline, 2-nitroimino-1, 3-diazacycloalkane motifs were designed and synthesized as plausible neonicotinoid analogues. These compounds were synthesized from 2-chloro/aryloxy-3-formyl quinolines and guanidine nitrate with the coupling of 2-chloro/aryloxy-3-(chloromethyl)quinolines, 2-nitroimino-1, 3-diazacycloalkanes under phase transfer catalysis (PTC) as crucial step. All the compounds were obtained in excellent yields (80–90%) and were characterized by 1H, 13C NMR and mass spectrometry. The newly generated compounds were screened for insecticidal activity against aphids in safflower field and some of them displayed moderate activity.
Design, synthesis and biological evaluation of mono- and bisquinoline methanamine derivatives as potential antiplasmodial agents
Bokosi, Fostino R.B.,Beteck, Richard M.,Mbaba, Mziyanda,Mtshare, Thanduxolo E.,Laming, Dustin,Hoppe, Heinrich C.,Khanye, Setshaba D.
, (2021/03/01)
Several classes of antimalarial drugs are currently available, although issues of toxicity and the emergence of drug resistant malaria parasites have reduced their overall therapeutic efficiency. Quinoline based antiplasmodial drugs have unequivocally been long-established and continue to inspire the design of new antimalarial agents. Herein, a series of mono- and bisquinoline methanamine derivatives were synthesised through sequential steps; Vilsmeier-Haack, reductive amination, and nucleophilic substitution, and obtained in low to excellent yields. The resulting compounds were investigated for in vitro antiplasmodial activity against the 3D7 chloroquine-sensitive strain of Plasmodium falciparum, and compounds 40 and 59 emerged as the most promising with IC50 values of 0.23 and 0.93 μM, respectively. The most promising compounds were also evaluated in silico by molecular docking protocols for binding affinity to the {0 0 1} fast-growing face of a hemozoin crystal model.
Design, Synthesis, and Antifungal Evaluation of Luotonin A Derivatives against Phytopathogenic Fungi
Chu, Qing-Ru,Du, Sha-Sha,He, Ying-Hui,Li, Hai-Xing,Liu, Ying-Qian,Tang, Chen,Wang, Jing-Ru,Wang, Ren-Xuan,Wu, Tian-Lin,Yang, Cheng-Jie,Zhang, Zhi-Jun
, p. 14467 - 14477 (2021/12/09)
Crop diseases caused by fungi threaten food security and exacerbate the food crisis. Inspired by the application of fungicide candidates from natural products in agrochemical discovery, a series of luotonin A derivatives were designed, synthesized, and evaluated for their antifungal activities against five plant fungi. Most of these compounds exhibited significant fungicidal activity against Botrytis cinerea in vitro with EC50 values less than 1 μg/mL. Among them, compounds w7, w8, w12, and w15 showed superior antifungal activity against B. cinerea with EC50 values of 0.036, 0.050, 0.042, and 0.048 μg/mL, respectively, which were more potent than boscalid (EC50 = 1.790 μg/mL). Preliminary mechanism studies revealed that compound w7 might pursue its antifungal activity by disrupting the fungal cell membrane and cell wall. Moreover, in vivo bioassay also indicated that compound w7 could be effective for the control of B. cinerea. The above results evidenced the potential of luotonin A derivatives as novel and promising candidate fungicides.
RETRACTED ARTICLE: Synthesis, Molecular Properties, and Biological Evaluation of Hybrid 1,2,3-Triazolylpolyaza Heterocyclic Compounds
Dasari, Srinivasa Rao,Tondepu, Subbaiah,Vadali, Lakshmana Rao,Ganivada, Mutyala Naidu,Seelam, Nareshvarma
, p. 195 - 208 (2019/01/04)
In this research article, a highly efficient, cost-effective synthesis of various hybrid molecules possessing 1,2,3-triazolyltetrazoles and evaluation of their biological activity have been addressed. The structure elucidation of these new library hybrid molecules has been carried out by IR, 1H NMR, 13C NMR, and mass spectral analysis. The compounds have been screened for their anticancer activity against human colon cancer cell line Colo-205 and human lung cancer cell line HOP-205, and the results attest that most of the compounds have shown very good therapeutic nature. In particular, compounds 3d, 3j, 6a, and 6e were more cytotoxic than Adriamycin against all tested human cancer cell lines with 68percent, 101.8percent, 94percent, and 104.5percent growth, respectively. In the present investigation, a series of 3a–j and 6a–h were subjected to molecular properties prediction, drug likeness by Molinspiration, and toxicity risks by Molsoft software programs. All the 18 analogues were chosen on the basis of Lipinski “Rule of five” for the synthesis, screening their antibacterial and anticancer as oral bioavailable drugs/leads.
Demonstration of in Vitro Resurrection of Aged Acetylcholinesterase after Exposure to Organophosphorus Chemical Nerve Agents
Zhuang, Qinggeng,Franjesevic, Andrew J.,Corrigan, Thomas S.,Coldren, William H.,Dicken, Rachel,Sillart, Sydney,Deyong, Ashley,Yoshino, Nathan,Smith, Justin,Fabry, Stephanie,Fitzpatrick, Keegan,Blanton, Travis G.,Joseph, Jojo,Yoder, Ryan J.,McElroy, Craig A.,Ekici, ?zlem Dogan,Callam, Christopher S.,Hadad, Christopher M.
, p. 7034 - 7042 (2018/06/13)
After the inhibition of acetylcholinesterase (AChE) by organophosphorus (OP) nerve agents, a dealkylation reaction of the phosphylated serine, referred to as aging, can occur. When aged, known reactivators of OP-inhibited AChE are no longer effective. Realkylation of aged AChE may provide a route to reversing aging. We designed and synthesized a library of quinone methide precursors (QMPs) as proposed realkylators of aged AChE. Our lead compound (C8) from an in vitro screen successfully resurrected 32.7 and 20.4% of the activity of methylphosphonate-aged and isopropyl phosphate-aged electric-eel AChE, respectively, after 4 days. C8 displays properties of both resurrection (recovery from the aged to the native state) and reactivation (recovery from the inhibited to the native state). Resurrection of methylphosphonate-aged AChE by C8 was significantly pH-dependent, recovering 21% of activity at 4 mM and pH 9 after only 1 day. C8 is also effective against isopropyl phosphate-aged human AChE.
Friedel-Crafts Chemistry. Part 48. Concise Synthesis of Condensed Azaheterocyclic [1,8]naphthyridinones, Azepino-, Azocino-, and Azoninoquinoline Systems via Friedel-Crafts Ring Closures
Abd El-Aal, Hassan A. K.
, p. 1082 - 1092 (2017/10/10)
Unprecedented construction of a novel series of quinoline heteropolycycles (tetracyclic keto-analogues of [1,8]naphthyridinones, azepino-, azocino-A nd azonino[2,3-b]quinolinones systems) 10a-i by Friedel-Crafts cycliacylation reactions is described. Starting heterocyclic acids precursors 3a-i were prepared from easily accessible 2-chloroquinoline-3-carbaldehyde 1 via a three different synthetic pathways. Acid-catalyzed ring closures of the resulting tosylated acids were achieved under the influence of both Br?nsted and Lewis acid catalysts. The present strategy enables a straightforward synthesis to fused tetracyclic quinolinone skeletons as demonstrated by concise and atom-economical syntheses.
Discovery of GBT440, an Orally Bioavailable R-State Stabilizer of Sickle Cell Hemoglobin
Metcalf, Brian,Chuang, Chihyuan,Dufu, Kobina,Patel, Mira P.,Silva-Garcia, Abel,Johnson, Carl,Lu, Qing,Partridge, James R.,Patskovska, Larysa,Patskovsky, Yury,Almo, Steven C.,Jacobson, Matthew P.,Hua, Lan,Xu, Qing,Gwaltney, Stephen L.,Yee, Calvin,Harris, Jason,Morgan, Bradley P.,James, Joyce,Xu, Donghong,Hutchaleelaha, Athiwat,Paulvannan, Kumar,Oksenberg, Donna,Li, Zhe
supporting information, p. 321 - 326 (2017/03/17)
We report the discovery of a new potent allosteric effector of sickle cell hemoglobin, GBT440 (36), that increases the affinity of hemoglobin for oxygen and consequently inhibits its polymerization when subjected to hypoxic conditions. Unlike earlier allosteric activators that bind covalently to hemoglobin in a 2:1 stoichiometry, 36 binds with a 1:1 stoichiometry. Compound 36 is orally bioavailable and partitions highly and favorably into the red blood cell with a RBC/plasma ratio of ～150. This partitioning onto the target protein is anticipated to allow therapeutic concentrations to be achieved in the red blood cell at low plasma concentrations. GBT440 (36) is in Phase 3 clinical trials for the treatment of sickle cell disease (NCT03036813).
Novel 1,3,4-oxadiazole motifs bearing a quinoline nucleus: Synthesis, characterization and biological evaluation of their antimicrobial, antitubercular, antimalarial and cytotoxic activities
Ladani, Gaurav G.,Patel, Manish P.
, p. 9848 - 9857 (2015/12/01)
A series of quinoline based 1,3,4-oxadiazole derivatives (8a-l) were synthesized by a chloro-amine coupling reaction approach with different catalysts and solvents. Substituted 1,3,4-oxadiazole intermediates 7a-c were obtained from 2-substituted-N-phenylh
Design of new hybrid template by linking quinoline, triazole and dihydroquinoline pharmacophoric groups: A greener approach to novel polyazaheterocycles as cytotoxic agents
Praveena, Koduru Sri Shanthi,Shivaji Ramarao, Edupuganti Veera Venkat,Murthy, Nandula Yadagiri Sreenivasa,Akkenapally, Surekha,Ganesh Kumar,Kapavarapu, Ravikumar,Pal, Sarbani
, p. 1063 - 1069 (2015/02/19)
A new hybrid template designed by linking three pharmacophoric groups, for example, quinoline, triazole and dihydroquinoline moieties have been used for the generation of a library of molecules as potential cytotoxic agents. Synthesis of these polyazaheterocycles were carried out by using a strategy that involved one-pot sequential azidation and CuAAC in water under mild conditions. A number of 1,4-disubstituted 1,2,3-triazoles possessing quinolinylmethylene at N-1 and 1,2-dihydroquinolinyl methylene at C-4 as different substituents were synthesized and evaluated for their cytotoxic effects against various cancer cells. Some of them showed encouraging activities against lung cancer cells and one of them showed inhibition of PDE4 indicating the potential medicinal value of these novel polyazaheterocycles.
Preparation and reactions of heteroarylmethylzinc reagents
Barl, Nadja M.,Sansiaume-Dagousset, Elodie,Monzon, Gabriel,Wagner, Andreas J.,Knochel, Paul
supporting information, p. 2422 - 2425 (2014/05/20)
We report a general preparation of heteroarylmethylzinc chlorides by direct zinc insertion into heteroarylmethyl chlorides, along with a facile and straightforward synthesis of these heterocyclic chloromethyl precursors. We demonstrate that heteroarylmethylzinc reagents undergo various reactions including cross-couplings, allylations, acylations, and addition reactions to aldehydes, leading to polyfunctional heterocyclic products. Furthermore, these heteroaromatic zinc compounds prove to be versatile reagents for the preparation of various N- and O-heterocycles and give access to an analogue of a CB1 modifier.
